One-pot synthesis of Eu-MOFs for bioimaging and drug delivery.

OBJECTIVE: The use of metal-organic framework (MOF) platforms has been a topic of growing interest in the fields of drug delivery and bioimaging. This study was designed to develop and evaluate a novel MOF-based drug and radiation delivery nanosystem. METHODS: Eu-MOFs were characterized in vitro via X-ray diffraction, scanning electronic microscopy, and FT-IR spectrometry. Nanocarrier uptake and associated cell viability were assessed using a CCK-8 assay and using a high content screening system. Biodistribution studies were conducted with a Luminal II IVIS imaging system to assess nanocarrier distribution in different organs. As such, paclitaxel was selected as a model drug in the present study to evaluate Eu-MOF drug loading and release characteristics in vitro via HPLC. RESULTS: A straightforward one-step approach was used to successfully fabricate sea urchin-shaped Eu-MOFs that were self-assembled from Eu3+ and 1,3,5-pyromellitic acid. These MOFs exhibited robust red fluorescence owing to the antenna effect. Owing to their fluorescent properties, these Eu-MOFs were able to facilitate in vivo imaging with a high quantum yield and low background signal. Importantly, our Eu-MOFs exhibited good biocompatibility, low cytotoxicity, and high imaging efficiency. As they exhibited slow-release kinetics and targeted biodistribution profiles, these Eu-MOFs additionally hold great promise as potential anti-cancer agents in clinical settings. CONCLUSION: Herein, we designed a novel Eu-MOF active targeted drug delivery nanocarrier platform and found that it represents a promising therapeutic tool for cancer treatment.

Lysophosphatidylcholine promotes intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells via an orphan G protein receptor 2-mediated signaling pathway.

The oxLDL-based bioactive lipid lysophosphatidylcholine (LPC) is a key regulator of physiological processes including endothelial cell adhesion marker expression. This study explored the relationship between LPC and the human umbilical vein endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with a particular focus on the regulation of the LPC-G2A-ICAM-1/VCAM-1 pathway in this context. We explored the LPC-inducible role of orphan G protein receptor 2 (G2A) in associated regulatory processes by using human kidney epithelial (HEK293) cells that had been transfected with pET-G2A, human umbilical vein endothelial cells (HUVECs) in which an shRNA was used to knock down G2A, and western blotting and qPCR assays that were used to confirm changes in gene expression. For in vivo studies, a rabbit model of atherosclerosis was established, with serum biochemistry and histological staining approaches being used to assess pathological outcomes in these animals. The treatment of both HEK293 cells and HUVECs with LPC promoted ICAM-1 and VCAM-1 upregulation, while incubation at a pH of 6.8 suppressed such LPC-induced adhesion marker expression. Knocking down G2A by shRNA and inhibiting NF-κB activity yielded opposite outcomes. The application of a Gi protein inhibitor had no impact on LPC-induced ICAM-1/VCAM-1 expression. Atherosclerotic model exhibited high circulating LDL and LPC levels as well as high aortic wall ICAM-1/VCAM-1 expression. Overall, these results suggested that the LPC-G2A-ICAM-1/VCAM-1 pathway may contribute to the atherogenic activity of oxLDL, with NF-κB antagonists representing potentially viable therapeutic tools for the treatment of cardiovascular disease.